Malignant transformation induced by chemial carcinogens is a stable heritable trait, yet neither the mechanism by which it is induced nor the character of the trait once it is expressed are known with certainty. It has been suggested that chemicals may induce transformation by causing either a somatic gene mutation or an epigenetic change in gene expression. Once induced, the transformation may be maintained either by the continued expression of some dominant transforming function or by the recessive loss of a function necessary to keep the cell normal. A genetic analysis of both the induction and expression of chemically induced transformation is planned to differentiate between these sets of alternatives. Correlations between mutation and transformation induced in vitro by chemical carcinogens will be sought to test the somatic mutation hypothesis in rodent and human cells. Chemically transformed clones will be analyzed by somatic cell hybridization to determine if transformation is a dominant or recessive trait and to obtain an estimate of the number of genes involved.